Fatty acids are a key component of many human metabolic processes and are an important fuel source. Fatty acids are stored in multiple tissues, and often transported within the body in the form of triglycerides (triacylglycerols). Derangements in fatty acid and triglyceride metabolism are characteristic of obesity, type 2 diabetes, dyslipidemia, non-alcoholic fatty liver disease, metabolic syndrome, and other metabolic diseases. A key player in the conversion of fatty acids to triglycerides is the microsomal enzyme diacylglycerol O-acyltransferase 1 (DGAT1). DGAT1 catalyzes the final and only committed step in triglyceride synthesis. More specifically, DGAT1 couples a fatty acid Coenzyme A ester with 1,2-diacylglycerol to produce a triglyceride and Coenzyme A. There are two known DGAT enzymes types 1 and 2, but there is little homology between the two. DGAT1 activity can be detected in a number of mammalian tissues including intestine, liver and adipose. DGAT1 is a key component of triglyceride synthesis in multiple tissues, in the absorption of dietary triglycerides, and in the hepatic synthesis and secretion of triglyceride rich lipoproteins. DGAT1 activity may influence the release of intestinal peptides such as Peptide YY (PYY) and Glucagon-like peptide-1 (GLP-1) which play an important role in metabolic processes. The DGAT1 (−/−) knockout mouse is lean and resistant to high fat diet-induced obesity and insulin resistance. These animals have a higher metabolic rate and increased activity relative to wild type mice. The phenotype of the DGAT1 (−/−) animal suggests that DGAT1 inhibitors may be useful for the treatment of a number of metabolic diseases including type 2 diabetes and obesity.
Therefore, the present invention provides a novel compound having a medical utility including inhibition of DGAT1 activity, which can be useful in the prevention or treatment of a disease, disorder or condition modulated by DGAT1 inhibition, such as obesity-related disorders, type 2 diabetes, or diabetes-related disorders.